The role of donor lymphoid cells in allogeneic marrow engraftment.
Current prophylaxis regimens do not provide satisfactory control of graft-versus-host disease (GVHD) in patients transplanted with unmodified marrow from an unrelated donor or from a related donor mismatched for more than one HLA antigen. Extensive T cell depletion of the donor marrow can eliminate the need for post-transplant immunosuppression and reduce the overall risk of GVHD to 10% or less with either HLA-identical or HLA-nonidentical transplantation, but this benefit is offset by an increased risk of graft failure. Evidence from clinical studies is consistent with the hypothesis that donor T cells help to eliminate or inactivate residual host lymphocytes surviving the preparative regimen and remaining capable of causing rejection, but the relationships between T cells that facilitate engraftment and those that cause GVHD have not been defined. Limited data from animal experiments have suggested that a marrow graft-enhancing effect can be mediated by cells that do not initiate GVHD and that GVHD per se does not necessarily enhance engraftment. One way that T cells could facilitate engraftment without causing GVHD is through 'veto activity'. Donor cells with this type of activity can specifically prevent an immune response when they are recognized by host T cells. Another way in which donor T cells might facilitate engraftment without causing GVHD is through production of lymphokines or cytokines that promote the growth and differentiation of hematopoietic stem cells. A third way is through a GVH effect on the host lymphoid cells responsible for rejection. The donor cells that mediate this effect might not cause GVHD if they recognize host alloantigens not expressed in the skin, liver or gut.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
P J
PJ
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
D016026:Bone Marrow Transplantation / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000502:physiology*; D014184:Transplantation, Homologous